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Biomedical subjects

Henri Portier

Publications and source records attributed to Henri Portier.

At least 19 recordsLinked to original sources
PubMed2006

Performance of a predictive rule to distinguish bacterial and viral meningitis.

OBJECTIVE: Although diagnostic performance has recently improved by using new diagnostic methodologies, acute patient management is usually initiated after considering only fairly elementary findings of CSF examination. Using these early findings it is often difficult to distinguish between bacterial and aseptic (viral) meningitis. In order to help distinguish these two categories, scoring tools have been proposed that are more or less complex and validated. METHODS: The aim of this study was to establish a simple scoring tool and compare it to other available decision making systems. We retrospectively analysed all the meningitis cases from our patients at our institution and established a scoring tool for pediatric meningitis and for meningitis in adults by using categorized analysis tree methodology. RESULTS: Main categories for bacterial etiology were, leucocytosis >15 giga, CSF leucocytes count >1700 per ml, CSF neutrophil percentage >80, CSF protein >2.3g/l and glucose CSF/blood ratio <0.33 for adults and CSF leucocytes count >1800, CSF neutrophil percentage >80, CSF protein >1.2g/l and glucose CSF/blood ratio <0.3 for children. Additionally, our new scoring tool and five published ones were compared using our data and two external data sets; from these scores, three, including ours, exhibited good sensitivity and specificity. We then performed several thousand Monte Carlo simulations of both bacterial and viral meningitis for children and adults. We found that our scoring tool (Meningitest) had very high performances with positive and negative predictive values of 97% and 94%, respectively. CONCLUSION: Thus, from this analysis of five meningitis scoring systems, we believe that our new tool is simple, does not need any complex calculation and is effective in identifying bacterial vs viral meningitis in fully immunocompetent children and adults.

Adult↗
PubMed2005

Low trough plasma concentrations of nevirapine associated with virologic rebounds in HIV-infected patients who switched from protease inhibitors.

BACKGROUND: The substitution of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) for protease inhibitors (PIs) has demonstrated its suitability to maintain virologic response. However, the switch from PIs to an NNRTI could fail for a number of reasons, including NNRTI-associated toxicity and emergence of NNRTI-resistant variants. OBJECTIVE: To describe the virologic failures among 74 HIV-infected patients who switched from PIs to nevirapine. METHODS: Virologic failure was defined as any rebound of the plasma HIV-RNA (pVL) levels >1000 copies/mL on one occasion or 2 consecutive intermittent viremia episodes defined as increases of the pVL >20 copies/mL but <1000 copies/mL. Virologic failures were investigated retrospectively by determining nevirapine trough concentrations and performing genotypic resistance analysis. RESULTS: The mean nevirapine concentration was significantly lower in patients with virologic failure in comparison with patients with virologic response (2572 +/- 1642 vs 4550 +/- 2084 ng/mL, respectively; p = 0.003). In multivariate analysis, the mean duration of undetectable pVL before the switch and the mean plasma concentration of nevirapine were significantly associated with virologic success with relative rates of 1.39 (95% CI 1.10 to 1.76, p = 0.006) and 2.7 (95% CI 1.37 to 5.41, p = 0.01), respectively. In patients with pVL >1000 copies/mL, nevirapine mutations and nucleoside reverse-transcriptase inhibitor mutations were found in 80% of the cases. CONCLUSIONS: The risk of virologic failure after the switch from PI to nevirapine is higher in cases of inadequate nevirapine plasma concentrations. Our data support prospective monitoring of nevirapine plasma concentrations to detect low concentrations prior to the emergence of resistance mutations.

Adult↗
PubMed2005

Community epidemiology of Chlamydia and Mycoplasma pneumoniae in LRTI in France over 29 months.

BACKGROUND: The role of Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) in lower respiratory tract infections (LRTI) is still little known in community settings. METHODS: In all, 3207 adult cases of LRTI (871 with pneumonia, and 2336 with acute bronchitis) were prospectively included in the ETIIC1 ETIIC : ETude de l'Incidence des Infections respiratoires basses d'origine Communautaire dues A Chlamydia pneumoniae et Mycoplasma pneumoniae (Incidence of CP and MP in LRTI in community settings) program by 303 general practitioners and 24 hospital physicians in France between September 1997 and February 2000. The polymerase chain reaction and immunoassays were used to detect CP or MP in 3198 pharyngeal specimens obtained by gargling. RESULTS: Of these 3198 patients, 232 (7.3%), were PCR-positive for CP and/or MP. Immunoassays were far less sensitive than PCRs (Se = 2 and 13% for MP and CP). Among the 2336 patients with acute bronchitis, PCR was positive for CP in 95 (4.1%), and for MP, in 54 (2.3%). Among the 671 patients with radiologically confirmed pneumonia, PCR was positive for CP in 23 (3.4%), and for MP in 49 (7.3%). CP and MP displayed significant geographic heterogeneity. Independent clinical determinants of positive PCR for CP and/or MP were age below 45 years, previous antimicrobial therapy (especially betalactams). Clinical signs were not of practical use in distinguishing accurately between etiologic diagnoses. CONCLUSIONS: CP or MP diagnosed by PCR were found in more than 7% of patients with LRTI in community settings with a significant geographical heterogeneity and significant temporal trends in the incidence.

Adult↗
PubMed2005

The impact of mechanical ventilation on the moxifloxacin treatment of experimental pneumonia caused by Streptococcus pneumoniae.

OBJECTIVE: Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and is responsible for early-onset ventilator-associated pneumonia as well. In intensive care units, community-acquired pneumonia is still associated with a mortality rate of up to 30%, especially when mechanical ventilation is required. Our objective was to study to what extent MV could influence the efficacy of moxifloxacin in a rabbit model of pneumonia. DESIGN: Prospective experimental study. SETTING: University hospital laboratory. SUBJECTS: Male New Zealand White rabbits (n = 75). INTERVENTIONS: S. pneumoniae (16089 strain; minimal inhibitory concentration for moxifloxacin = 0.125 mg/L) was instilled intrabronchially. Four hours later, a human-like moxifloxacin treatment was initiated in spontaneously breathing (SB) and mechanically ventilated (MV) animals. Untreated rabbits were used as controls. Survivors were killed 48 hrs later. Pneumonia was assessed and moxifloxacin pharmacokinetics were analyzed. MEASUREMENTS AND MAIN RESULTS: Moxifloxacin treatment was associated with an improvement in survival in the SB animals (13 of 13 [100%] vs. eight of 37 [21.6%] controls). The survival rate was less influenced by treatment in MV rabbits (seven of 15 [46.1%] vs. one of eight [12.5%] controls). The lung bacterial burden was greater in MV compared with SB rabbits (5.1 +/- 2.4 vs. 1.6 +/- 1.4 log10 colony-forming units/g, respectively). Nearly all the untreated animals presented bacteremia as reflected by a positive spleen culture. No bacteremia was found in SB animals treated with moxifloxacin. In contrast, three of 13 (23.1%) moxifloxacin-treated and MV animals had positive spleen cultures. The apparent volume of distribution of moxifloxacin was lower in MV compared with SB rabbits. CONCLUSIONS: In our model of moxifloxacin-treated S. pneumoniae pneumonia, mechanical ventilation was associated with a higher mortality rate and seemed to promote bacterial growth as well as systemic spread of the infection. In addition, the volume of distribution of moxifloxacin was reduced in the presence of mechanical ventilation. Although the roles of factors such as anesthesia, paralysis, and endotracheal tube insertion could not be established, these results suggest that mechanical ventilation may impair host lung defense, rendering antibiotic therapy less effective.

Animals↗
PubMed2005

[Urinary bovine tuberculosis in man].

Human infestation by Mycobacterium bovis has become rare since eradication of bovine tuberculosis. However, this aetiology must be envisaged, as the sensitivity of the micro-organism is variable and its demonstration requires specific techniques.

Animals↗
PubMed2004

Influence of positive end-expiratory pressure (PEEP) on histopathological and bacteriological aspects of pneumonia during low tidal volume mechanical ventilation.

OBJECTIVE: Ventilatory strategies combining low tidal volume (V(T)) with positive end-expiratory pressure (PEEP) are considered to be lung protective. The influence of the PEEP level was investigated on bacteriology and histology in a model of ventilator-associated pneumonia. SUBJECTS: Nineteen New Zealand rabbits. INTERVENTIONS: The animals were mechanically ventilated with a positive inspiratory pressure of 15 cmH(2)O and received either a zero end-expiratory pressure (ZEEP, n=6), a 5 cmH(2)O PEEP (n=5) or a 10 cmH(2)O PEEP (n=4). An inoculum of Enterobacter aerogenes was then instilled intrabronchially. The non-ventilated pneumonia group (n=4) was composed of spontaneously breathing animals which received the same inoculum. Pneumonia was assessed 24 h later. MAIN RESULTS: The lung bacterial burden was higher in mechanically ventilated animals compared with spontaneously breathing animals. All animals from the latter group had negative spleen cultures. The spleen bacterial concentration was found to be lower in the 5 cmH(2)O PEEP group when compared to the ZEEP and 10 cmH(2)O PEEP groups (3.1+/-1.5 vs 4.9+/-1.1 and 5.0+/-1.3 log(10) cfu/g, respectively; p<0.05). Lung weight and histological score values were lower in the spontaneously breathing animals as well as in the 5 cmH(2)O PEEP group compared with the ZEEP and 10 cmH(2)O groups. CONCLUSIONS: Mechanical ventilation substantially increased the lung bacterial burden and worsened the histological aspects of pneumonia in this rabbit model. Variations in terms of lung injury and systemic spreading of infection were noted with respect to the ventilatory strategy.

Animals↗
PubMed2004

Effect of low-level resistance on subsequent enrichment of fluoroquinolone-resistant Streptococcus pneumoniae in rabbits.

BACKGROUND: We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window. METHODS: Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility. RESULTS: Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not. However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined. CONCLUSIONS: A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements.

Animals↗
PubMed2004

In vivo pharmacodynamic efficacy of gatifloxacin against Streptococcus pneumoniae in an experimental model of pneumonia: impact of the low levels of fluoroquinolone resistance on the enrichment of resistant mutants.

OBJECTIVES: To investigate the impact of low levels of fluoroquinolone resistance on the emergence of resistant mutants, we examined the mutant selection window (MSW) hypothesis in experimental pneumonia in rabbits infected with pneumococci with various susceptibility levels to fluoroquinolones and treated with gatifloxacin using a human-like regimen (equivalent to 400 mg once daily). The MSW corresponds to the range of concentrations between the minimal inhibitory concentration (MIC) and the mutant prevention concentration (MPC), which is the antibiotic concentration that prevents selection of resistant mutants. MATERIALS AND METHODS: Five pneumococcal strains were tested and were defined as follows [MIC of ciprofloxacin (mg/L)/MIC of gatifloxacin (mg/L)/MPC of gatifloxacin (mg/L)/involved quinolone resistance mechanisms]: strain 16089=0.5/0.25/0.25/wild-type; strain MS1A=2/0.5/1/efflux; strain MS2A=8/1/8/parC S79F; strain MR3B4=10/1/8/parC S79T; strain Gyr-1207=6/4/4/gyrA S81F. RESULTS: A 48 h human-like treatment with gatifloxacin was significantly bactericidal on pneumonia induced by strain 16089 ( > 6 log(10) killing) as well as the efflux derivative strain MS1A ( > 5 log(10) killing). However, a small number of parC-gyrA mutants were recovered in 26% of the animals infected with this efflux strain. As expected, no decrease in viable bacteria counts was observed when pneumonia was induced by the gyrA resistant strain. In contrast, because of the enrichment of highly resistant mutants in 100% of the animals, no significant bacterial reduction was observed after treatment of pneumonia induced by the two susceptible parC mutated strains. A classification and regression tree (CART) analysis identified T(MSW) (percentage of the time during which gatifloxacin serum concentrations are inside the MSW) and AUC(MSW) (area under curve between MIC and MPC values) as the best parameters associated with the enrichment of resistant pneumococci. CONCLUSIONS: This study shows that the acquisition of a low level of fluoroquinolone resistance (especially a parC mutation and to a lesser extent an efflux mechanism) is associated with a clearly lower potential for preventing resistance development. These data support the concept that resistant mutants are selectively enriched when antibiotic concentrations fall inside the mutant selection window and suggest that in vivo dynamic models have to be used to predict the relative abilities of quinolones to prevent mutant selection.

Animals↗
PubMed2004

Clinical, immunological and virological evolution in patients with CD4 T-cell count above 500/mm3: is there a benefit to treat with highly active antiretroviral therapy (HAART)?

To assess the clinical, immunological and virological evolution in HIV-1 infected patients with CD4 T-cell count above 500/mm3, a historical cohort of 202 untreated and 96 patients treated with HAART was longitudinally studied (median follow-up 36 months). Fourteen untreated and 2 treated patients experienced clinical progression (p = 0.09). The difference between baseline CD4 T-cell count and after 3 years, was -240/mm3 in the untreated group +19/mm3 in the HAART group (p < 10(-3)). A better immunological outcome was significantly associated with a HIV sexual contamination (p = 0.01), HAART (p = 0.01), high baseline CD4 T-cell count (p < 10(-3)) and low baseline HIV viral load (p = 0.01). In the HAART group, the incidence rate of antiretroviral modification due to tolerance difficulties was 0.23+/-0.36/patient year. A sustained undetectable HIV viral load was correlated with a low baseline HIV viral load (p = 0.003) and to be antiretroviral naive (p < 10(-3)). Thus, HAART provide a better immunological outcome in patients with high CD4 T-cell count. However, the CD4 decay slope after 3 years, the risk of therapeutic side-effects and the low risk of clinical progression do not support systematic treatment of those patients.

Adult↗
PubMed2004

Bilateral facial palsy in a case of leptospirosis.

When returning from a 5-month trip to China, a 21-y-old Dutch male developed clinical signs, symptoms, and an antibody response compatible with leptospirosis. On d 15 of disease, he also developed facial palsy with a bilateral Bell's phenomenon. Facial palsy is a rare finding in leptospirosis, and if a causal relation exists, the delay of onset in the present case would suggest vasculitis rather than a direct neurotoxic effect.

Adult↗
PubMed2004

Mutant selection window in levofloxacin and moxifloxacin treatments of experimental pneumococcal pneumonia in a rabbit model of human therapy.

For some pneumococci the fluoroquinolone MICs are low but the mutant prevention concentrations (MPCs) are high; this difference defines in vitro the mutant selection window (MSW). We investigated in vivo the bacterial reduction and the occurrence of resistant mutants with moxifloxacin (MFX; 400 mg once daily) or levofloxacin (LVX; 500 mg twice daily) in treatments similar to those in humans with experimental pneumonia due to pneumococci (expPP) exhibiting various MICs and MPCs. The MIC/MPC for MFX and LVX and genotypes were as follows: strain 16089, 0.125/0.125 and 0.5/0.5 (wild type); strain MS1A, 0.25/0.25 and 1/2 (efflux); strain MS2A, 0.25/4 and 1.75/28 (parC79); strain MR3B4, 0.25/4 and 2/32 (parC79); strain M16, 0.5/2 and 8/32 (parC83); strain Gyr-1207, 1.5/3 and 8/16 (gyrA); and strain MQ3A, 4/4 and 16/64 (parC and gyrA). Both drugs were efficient with wild type-expPP, but only MFX was efficient with efflux-expPP. No bacterial reduction was observed for parC-expPPs due to mutants observed in 18 to 100% of animals, depending on the strain and the drug tested. These mutants showed unbound area under the concentration-time curve and MICs of from 50 to 164 for MFX. The in vivo pharmacodynamic boundaries of the MSW were different for MFX and LVX. We conclude that, after LVX or MFX treatment, mutants occur in vivo if there is a preexisting parC mutation, since the drug concentrations fall below the MPCs of these strains. Since the MPC determination cannot be routinely determined, these phenotypes or genotypes should be detected by simple tests to guide the therapeutic options.

Animals↗
PubMed2003

Candidemia in critically ill patients: difference of outcome between medical and surgical patients.

OBJECTIVE: Candidemia is increasingly encountered in critically ill patients with a high fatality rate. The available data in the critically ill suggest that patients with prior surgery are at a higher risk than others. However, little is known about candidemia in medical settings. The main goal of this study was to compare features of candidemia in critically ill medical and surgical patients. DESIGN: Ten-year retrospective cohort study (1990-2000). SETTING: Medical and surgical intensive care units (ICUs) of a teaching hospital. PATIENTS: Fifty-one patients with at least one positive blood culture for Candida species. MAIN RESULTS: Risk factors were retrieved in all of the patients: central venous catheter (92.1%), mechanical ventilation (72.5%), prior bacterial infection (70.6%), high fungal colonization index (45.6%). Candida albicans accounts for 55% of all candidemia. The overall mortality was 60.8% (85% and 45.2% in medical and surgical patients, respectively). Independent factors associated with survival were prior surgery (hazard ratio [HR] =0.25; 0.09-0.67 95% confidence interval [CI], p<0.05), antifungal treatment (HR =0.11; 0.04-0.30 95% CI, p<0.05) and absence of neutropenia (HR =0.10; 0.02-0.45 95% CI, p<0.05). Steroids, neutropenia and high density of fungal colonization were more frequently found among medical patients compared to surgical ones. CONCLUSIONS: Candidemia occurrence is associated with a high mortality rate among critically ill patients. Differences in underlying conditions could account for the poorer outcome of the medical patients. Screening for fungal colonization could allow identification of such high-risk patients and, in turn, improve outcome.

APACHE↗
PubMed2003

[Acute Gemella haemolysans spondylodiscitis in an immunocompetent patient].

INTRODUCTION: Gemella is a commensal bacterium of the upper respiratory tract responsible for rare infections such as acute endocarditis and meningitis. We report the case of an acute Gemella haemolysans spondylodiscitis. OBSERVATION: A 72 year-old woman was hospitalised for an etiological control and treatment of acute L4-L5 spondylodiscitis with epiduritis, confirmed on MRI. The clinical picture was composed of backache with shivering and alteration in general status of health. The peripheral bacteriological samples, intra-dermal reaction and brucella serology were all negative. The surgical L5 biopsy, following bacteriological enrichment, isolated Gram-positive cocci, later identified as Gemella haemolysans. The antibiogram showed good sensitivity to amoxicillin, dalacin and erythromycin, and strong resistance to aminosides. The search for a contamination point was negative. The patient rapidly improved with antibiotics combining 6 g/d of amoxicillin and 1200 mg/d of clindamycin, and the biological and clinical signs regressed. The antibiotic bi-therapy was continued for two and a half months and then relayed to amoxicillin alone for two further weeks. COMMENTS: The first descriptions of Gemella haemolysans infection were made in the seventies. Cases of infectious endocarditis were succeeded by septicaemia on cirrhosis and later a few cases of acute post-neurosurgical meningitis. In the majority of cases, a dental contamination point was found. The difficulties in its etiological diagnosis, related to the problems in identifying this germ that has similar characteristics to Streptococcus viridans, suggests that the prevalence of Gemella haemolysans infections is greatly underrated. The sensitivity profile generally observed is sensitivity to penicillins and aminosides--the association of which is synergic--, to cyclines and glycopeptides, and resistance to trimethoprime-sulfamethoxazole.

Acute Disease↗
PubMed2003

Increased VLDL-apoB and IDL-apoB production rates in nonlipodystrophic HIV-infected patients on a protease inhibitor-containing regimen: a stable isotope kinetic study.

The aim of this study was to identify the first abnormalities of apolipoprotein B (apoB) metabolism in HIV-infected patients treated by antiretroviral therapy (ART) with protease inhibitors (PIs). The influence of ART on the metabolism of apoB in VLDL, IDL, and LDL was investigated in six patients receiving dual nucleoside reverse transcriptase inhibitors (NRTIs) and PI, and in five patients receiving NRTI and nevirapine. None of the patients had lipodystrophy. The study was performed in the fed state. Each subject received an intravenous injection of a 0.7 mg.kg-1 bolus of l-[1-13C]leucine, immediately followed by a 16 h constant infusion at 0.7 mg.kg-1.h-1. The VLDL- and IDL-apoB concentrations were significantly higher in PI-treated patients compared to non-PI-treated patients. The VLDL-apoB and IDL-apoB production rates were markedly higher in PI-treated patients compared to non-PI-treated patients (54.5 +/- 30.1 vs. 30.9 +/- 8.4 mg.kg-1.d-1, P = 0.04; and 43.5 +/- 20.0 vs. 18.7 +/- 7.8 mg.kg-1.d-1, P = 0.04, respectively). In conclusion, our study shows that patients receiving ART with PI present altered metabolism of the VLDL-IDL-LDL chain compared with patients treated without PI. These data confirm that PI therapy is associated with a physiopathological mechanism for dyslipidemia in addition to the effect of lipodystrophy on lipid metabolism.

Adult↗
PubMed2003

[New strategies for angina case management in France].

Old French recommendations were to treat all pharyngitis cases to prevent acute rheumatic fever. 85 to 90% of cases were treated (8 to 9 millions/year), of which 3/4 unnecessary. Furthermore, penicillin V the drug of first choice was prescribed only to 5 to 10% of patients. Considering the preocupating increase of bacterial resistances and the disponibility of performane Group A Beta-Hemolytic Streptococcus Rapid Diagnostic Test (Negative Predictive Value above 95%), the new management strategy is proposed in two ways. Firstly, the free delivery of RDT to practitioners which was associated in Burgundy with a dramatic prescription decrease to 41% without benefice lost for patients. Considering these good results the French authorities decided the generalization of RDT use in 2002 and more than 15,000 practitioners have been concerned by the formations delivered in 3 months. Secondly, the short course treatment assays initiated by our group have been validated and since 2002 the AFSSAPS recommend the preferential use of compounds which obtained the authorization of use in short course with a new indication incitating to document GABHS pharyngitis by the RDT use.

Adolescent↗